Many different metalloproteinase enzymes are involved in connective tissue degradation or breakdown, such as collagenase, stromelysin and gelatinase. Inhibitors of matrix degrading metalloproteinases (MMP's) are known to be useful in the treatment or prophylaxis of conditions involving such tissue degradation. Such diseases include rheumatoid arthritis, osteoarthritis, arthropathy, dermatological conditions, bone resorption, inflammatory diseases, tumor invasion or metastasis, in the promotion of wound healing, osteoporosis, rheumatoid arthritis, periodonititis, gingivitis, and corneal ulceration, gastric ulceration.
A number of hydroxamic acid derivatives have been suggested as being useful as collagenase inhibitors, or for promoting tumor regression, such as those in the following patents and patent applications: U.S. Pat. No. 4,599,361; EP 236872; WO 90/05716; WO 91/02716; WO 90/05719; WO 93/20047; EPO 0 498 665 A1; and WO 93/21942.
These compounds, however, have generally poor pharmacokinetic properties and or poor water solubility. Therefor a need still exists to identify novel compounds which overcome these deficiencies.